Meta-analysis of thrombolytics in 100 000 patients with acute MI
Recent years of clinical research have been devoted to the quest for optimal thrombolytic strategies, but what have we learned from past experience? German investigators M. Grunewald and E. Seifried set out to answer this question in their meta-analysis of 300 clinical trials involving 100 000 patients with acute myocardial infarction (MI).
The researchers reviewed the influence of early vs late initiation of conjunctive heparin therapy and compared the relative efficacy of currently available plasminogen activators. They consider that second generation plasminogen activators, in particular IV alteplase (rt-PA), are significantly superior to all other currently employed thrombolytic therapies, provided that an effective concomitant antithrombotic treatment is administered.
Say Grunewald and Seifried: 'it has become evident, that an effective thrombolytic strategy must include an effective antithrombotic treatment' , individually tailored to fit each strategy.
Confinnation from the GUSlO trial The researchers tested the reliability of their
meta-analysis by submitting their results prior to the presentation of the prospective GUSTO trial. *
Results from the German meta-analysis indicated a 60% reduction in relative hospital mortality risk with a patent vs an occluded infarct vessel at 90 minutes. Patency rates at 90 min were 15-20% higher with IV alteplase compared with streptokinase administration, according to these investigators. Thus, given that 90 min patency is a study endpoint of predictive value and that results of a retrospective data analysis are reliable, IV alteplase plus early heparin therapy in patients with acute MI should result in a 20% reduction in hospital mortality risk (in comparison with IV streptokinase plus early heparin).
The GUSTO trial reported a corresponding reduction of mortality risk of 14% with the superior alteplase regimen, which, Grunewald and Seifried say, confirms their meta-analysis results. *see Inpharma 917: 11. 11 Dec 1993; 8fXJ236304
Griinewald M. Seifried E. Meta-analysis of all available published clinical trials (19581990) on thrombolytic therapy for AMI: relative efficacy of different
therlIpeutic sttategies. Fibrinolysis 8: 67-86, Mar 1994 0""'''33